The purpose of this study is to assess the safety and effectiveness of AZD4547 in combination with fulvestrant vs. fulvestrant alone in ER+ breast cancer patients with FGFR1 polysomy (FISH4/5) or gene amplification (FISH 6)

Safety Run-in: Safety and tolerability in terms of number of patients with Adverse events (serious and non-serious) [ Time Frame: Adverse events recorded from patient screening to discontinuation from study plus 28 days safety follow-up ] [ Designated as safety issue: Yes ]

Safety Run-in: To investigate the Pharmacokinetics(PK)/Pharmacodynamics(PD) of AZD4547 and exemestane when given in combination by measuring blood plasma concentrations [ Time Frame: Blood sample taken on last day of exemestane monotherapy and Cycle 1 day 7 (AZD4547+exemestane), (sampling time: pre-dose to 10-12h) ] [ Designated as safety issue: No ]

Safety Run-in: Measure the effects of AZD4547 on circulating oestradiol [ Time Frame: Blood sample for oestradiol level taken at screening, on last day of exemestane monotherapy and day 7 of cycle 1 ] [ Designated as safety issue: No ]

Randomized phase IIa: Measurement in the change of tumor size at week 12 across the two arms as measured by RECIST. [ Time Frame: RECIST assessment at baseline and week 12. ] [ Designated as safety issue: No ]

Randomized phase IIa: Measurement of Objective Response Rate (ORR) (the percentage of patients with at least one visit response). As measured by RECIST. [ Time Frame: RECIST assessment at baseline, week 12 and then every 8 weeks until objective disease progression ] [ Designated as safety issue: No ]

Randomized phase IIa: Duration of Response (DoR) the time taken from first response until progression or death. As measured by RECIST. [ Time Frame: RECIST assessment at baseline, week 12 and then every 8 weeks until progression. ] [ Designated as safety issue: No ]

Randomized phase IIa: Measurement of the percentage of patients without progressive disease at 12 weeks. [ Time Frame: RECIST assessment at Baseline and week 12 ] [ Designated as safety issue: No ]

Randomized phase IIa: Measurement of the laboratory changes in clinical chemistry, haematology and urine as compared to baseline [ Time Frame: Laboratory data will be collected from screening to 28 days post drug discontinuation. ] [ Designated as safety issue: Yes ]

Randomized phase IIa: Measurement of changes in vital signs compared to baseline. [ Time Frame: Vital signs will be recorded from screening to 28 days after study drug discontinuation ] [ Designated as safety issue: Yes ]

Randomized phase IIa: Measurement of Health Related Quality of Life using a Cancer Quality of Life Questionnaire. [ Time Frame: Questionaire collected at screening and at each visit up to 28 days post discontinuation of study drug. ] [ Designated as safety issue: Yes ]

Safety run-in: Relapsing during/within 12 months of completion of a single regimen of adjuvant endocrine therapy with non-steroidal AI and/ tamoxifen or progression following 1st line endocrine therapy with non-steroidal AL

Rand phase IIa: Received at least 1 prior endocrine therapy in the metastatic setting or have relapsed during/ within 6 months of completion of adjuvant endocrine therapy (either non-steroidal AI or tamoxifen or a combination of both). Chemotherapy administered in the adjuvant setting is permitted.

Rand phase IIa: Mandatory provision of tumour sample to confirm FGFR1 polysomy or gene amplification. At least one measurable lesion that can be accurately assessed by CT/MRI/x-ray at baseline and follow up visits

History of hypersensitivity to active or inactive excipients of AZD4547 or exemestane (safety run-in ) or fulvestrant (Randomized phase), including castor oil, or drugs with a similar chemical structure or class to AZD4547 or exemestane or fulvestrant.

Randomized phase IIa: bleeding/blood clotting conditions that would prevent the administration of the fulvestrant injection into the buttocks

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01202591